Cystic Fibrosis: Tests, Treatments Improve Survival

by Food and Drug Administration (FDA)

Alex Deford had been ill almost from the moment of her birth on Oct. 30, 1971. Her frequent colds and ear infections coupled with her small size, despite a healthy appetite, prompted doctors to vaguely diagnose "failure to thrive." When Alex developed double pneumonia at 4 months, it was clear that something was very wrong.

That something turned out to be cystic fibrosis, the most common inherited illness among white people of Northern and Western European ancestry, although it is seen in all ethnic groups. Symptoms include thick, sticky mucus clogging the lungs, impairing breathing and attracting infection; a blocked pancreas that cannot release digestive enzymes, causing pain after eating; stubbed fingers from poor circulation; infertility; salty sweat; and other problems. Patients may have any or all of these symptoms — Alex had quite a list.

When she was diagnosed at Boston Children's Hospital early in 1972, Alex was so ill that she was expected to live only days. She survived eight years, but not easily.

Alex began each day by inhaling a decongestant. Then her parents took turns providing "postural drainage," a 30- to 60- minute pounding and pressing on each of 11 segments of the lungs, to loosen the mucus, which she coughed up. Alex would then take drugs — antibiotics to prevent lung infection and powdered digestive enzymes mixed into applesauce.

Despite this daily regimen, Alex died in January 1980. Her father, sportswriter and commentator Frank Deford, tells her story in his book, Alex, the Life of a Child.

Cystic fibrosis (CF) is inherited and affects 30,000 Americans. In 1989, scientists discovered the gene that causes cystic fibrosis (see accompanying article.) This discovery is enabling researchers to develop new diagnostic tests that will help identify those who can benefit from traditional as well as several new treatment approaches being evaluated by FDA. How CF Is Inherited

CF is typically passed from parents who each carry the gene, to children of either sex. Carriers have one faulty copy of the gene, which is responsible for the illness, plus one normal copy, which prevents symptoms. Each child of carrier parents has a 1 in 4 chance of inheriting CF; a 1 in 4 chance of being completely free of the mutant gene; and a chance of 1 in 2 of being a carrier, like the parents.

Couples usually learn that they carry CF when they have an affected child. By 1985, individuals who had a sibling with CF could find out if they carried the gene by taking a "genetic marker" (linkage analysis) test that spots a particular family's CF-carrying chromosome, but not the gene itself. Finding the CF gene makes it possible to detect most carriers, even if there are no affected relatives.

The Office of Technology Assessment estimates that 100 million to 200 million people in the United States might want to take a CF carrier test. About 8 million people in the United States, or 1 in 25 whites, may be carriers.

Diagnosing CF

The same gene discovery that has led to development of carrier tests is expected to help to more quickly diagnose CF, whose symptoms resemble those of other illnesses.

The most widely used and best-known CF test is the electrolyte sweat test. It detects the excess sodium, potassium and chloride (charged chemicals called electrolytes) found on the skin of many people with CF. A physician would perform a sweat test in a child with unexplained failure to gain weight, or with very frequent respiratory infections.

The sweat test evolved from the observations made by a physician, Dr. Paul di Sant'Agnese, during a 1953 heat wave in New York City. He was curious why so many children with CF were being brought to Babies and Children's Hospital, where he worked, with heat prostration. The youngsters were unable to cope with the heat because too much salt exited their bodies in sweat. The fact that the sweat of a person with CF contains two to six times as much salt as normal sweat gave him the idea for the sweat test.

The sweat test became widely used by the mid-1950s, and is the only CF test cleared by FDA for marketing. (A forerunner of the sweat test was the observation that a child's brow was salty when kissed. At the turn of the century, this is how midwives identified babies with cystic fibrosis.)

Although the sweat test is a critical part of a CF diagnostic work-up, salty sweat can indicate any of several disorders. Other tests help focus the diagnosis. Some of these tests are based on methodologies developed by reference laboratories, which perform medical tests and send the results to physicians. According to Freda Yoder of FDA's Center for Devices and Radiological Health, methodologies developed in- house have not traditionally been regulated by the agency.

Explains Tom Tsakeris, director of the division of clinical laboratory devices at FDA, "FDA regulates products, not laboratories. As long as they are not marketing the test itself, we do not regulate the lab." However, he adds, the Clinical Laboratory Improvement Act, signed into law in 1988 but not yet fully implemented, will regulate reference laboratories.

One test developed by reference labs measures the amount of the protein trypsinogen in a newborn's blood. Trypsinogen is manufactured by the pancreas and sent to the intestine, where it is snipped to a shorter form, trypsin, which helps digest proteins. If the pancreas is clogged by the sticky mucus of CF, trypsinogen levels are elevated, because the longer protein cannot be cut down to size.

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